Annual Medical Student Research Forum

Permanent URI for this collectionhttps://hdl.handle.net/2152.5/1482

This collection contains posters and related content from the Annual Medical Student Research Forums. The Annual Medical Student Research Forum began in 1962. Citations for items published from 2021 to the present are formatted according to the Publication Manual of the American Psychological Association, 7th edition, ©2020. (Older citations are formatted according to the Publication Manual of the American Psychological Association, 6th edition, ©2010.)

Booklets prior to 2013 are available in the archives. Contact archives@utsouthwestern.edu to make an appointment to access the earlier printed booklets.

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The 62nd Annual Medical Student Research Forum was held January 30, 2024. Selected posters are now available in this collection.

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6-year Pulmonary Lobectomy Analysis Comparing Robotic to Thoracotomy and VATS: Impact to a State University Cardiothoracic Training Program
(2017-01-17) Nawalaniec, James; Kernstine, Kemp; Elson, Matthew; Yuan, Chaofan; Madrigales, Alejandra; Lysikowski, Jerzy
OBJECTIVE: Current understanding of robotic lobectomy is largely from established thoracic surgical programs, often single-surgeon experience and does not involve trainees. Our objective is to assess the effect that a new robotic lobectomy program might have on a state university cardiothoracic (CT) training program to patient care, CT training, and the institution. METHODS: Our IRB-approved, prospectively maintained database and query of anatomic lung resections between 1/1/2006 to 6/30/2016 was verified with the medical center EMR and further verified with blinded double-entry. Inclusion criteria required a documented anatomic resection. Cost and oncologic data was obtained from the analytics department and tumor registry, respectively. Propensity scores were assigned based on age, sex, and five comorbidities. Lung cancer survival was analyzed by the Kaplan-Meier method and compared to the SEER database. Our robotic CT training method consists of a 6-month program over 3 years; the first 3 months focus on simulation and bedside-assist and the last 3 months, on complete case set-up and console training; adjustments made dependent upon the trainees' prior minimally invasive experience. RESULTS: 523 consecutive cases were identified, 91 cases were excluded. The query identified 212 robotic (179 non-small cell lung cancer (NSCLC)), 160 thoracotomy (117 NSCLC) and 60 video-assisted (VATS) (44 NSCLC) cases. Multiple surgeons performed each approach. Operative results and clinical outcomes favored robotic surgery compared to thoracotomy and showed little difference with VATS. Robotics increased lymph node stations, nodes, and upstaging rates, with similar R0 compared to thoracotomy and VATS; there was no significant difference in survival. A CT resident served as the console surgeon in 35% of all cases: 0% in the first two years increasing to 79% in the latest year. Minimally invasive surgeries increased from 32% of all cases in the first year of robotics to 89% in the latest year. The total volume of lung cancer treated at the center increased by 51%, surgical cases by 220%, and clinical trial accrual by 92%, since introducing robotics. CONCLUSION: A robotic surgery training component can be implemented at a state university cardiothoracic training program without sacrificing quality. Robotic surgery in this setting offers the same or better clinical results, is cost-effective, and is oncologically-sound. Additionally, a robotic program may increase an institution's lung cancer volume, enhancing both the CT resident training experience and clinical research. This analysis has also identified opportunities to further improve efficiency and reduce cost.
AB1-42 Antibody Producing Plasma Cells in DNA AB42 Trimer Immunized Mice Reside Predominantly in the Bone Marrow
(2013-01-22) Zacharias, Tresa; Langworthy, Suzanna; Fu, Min; Anderson, Larry; Stuve, Olaf; Rosenburg, Roger; Lambracht-Washington, Doris
Alzheimer's disease (AD) is the most common form of age-related dementia and affects nearly 40 million people worldwide. Immunotherapy provides a possible avenue for prophylaxis of AD, but a clinical trial (AN1792) in which patients with early AD were immunized with Aβ1-42 peptide was halted after the occurrence of meningoencephalitis in 6% of the immunized people which was attributed to a T cell autoimmune response. DNA vaccination has been shown to have a polarized Th2 immune response that lacks many of the features responsible for inflammation seen in peptide immunizations. In this study, we show a new feature of the DNA Aβ42 trimer elicited B cell immune response and present data for the presence of a long lived plasma cell pool residing within the bone marrow in DNA immunized mice but not in peptide immunized mice. Two groups of mice were analyzed: one group of B6C3F1 mice (n=20) were studied 4 months after the last DNA vaccination, and a second group of BALB/c mice (n=14), which received DNA or peptide immunizations, were analyzed 10 days following the last immunization. The comparison of antibody producing cells in bone marrow and spleen for the DNA and peptide immunized mice with an Antibody Forming Cell (AFC) ELISPOT assay and subsequent ELISAs showed that bone marrow plasma cells from DNA immunized mice produced more anti-Aβ42 IgG producing cells and higher levels of secreted IgG antibodies. In peptide immunized mice, more IgG antibody producing cells were found to reside in the spleen. These data indicate that the bone marrow may be an important reservoir for B cells following DNA Aβ42 immunization and is in line with studies showing that the bone marrow represents an excellent niche for the survival of long lived plasma cells and a lifetime source for antibody producing B cells which are independent of continuous antigen specific stimulation. Further studies are needed to show whether it is possible to define additional phenotypic characteristics for the antigen specific B cell immune response in DNA Aβ42 trimer immunized mice or differences in the TH subsets directly involved in initial signaling events to B cells in the germinal center reactions.
Abdominal Based Free Flap Breast Reconstruction: Stratifying Complications with Perforator Numbers
(2017-01-17) Wang, Jenny; Zhou, Michael; Kayfan, Samar; Teotia, Sumeet S.; Haddock, Nicholas T.
BACKGROUND: Single perforator flaps in breast reconstruction have been reported to have increased fat necrosis. We were motivated to evaluate our experience and the effect of number of perforators on DIEP flap complications and donor site morbidity. METHODS: 199 patients underwent 328 DIEP flaps by two surgeons from 2010 to 2016 at a university hospital. Perforator selection was guided by CT imaging and clinical observation. First, perforator average size was compared among flaps with 1 perforator (n= 110 flaps), 2 perforators (n= 136 flaps), and 3 perforators (n= 82 flaps). Next, rates of fat necrosis, flap failure, and abdominal bulging were analyzed among the same three perforator groups. In addition, rates of postoperative abdominal bulge requiring surgical intervention was compared to the presence of a nerve-preserving type flap harvest. RESULTS: Average perforator size significantly decreased as the number of perforators increased (1 perforator = 2.11mm, 2 perforators = 1.80mm, 3 perforators = 1.65mm, p-value = 0.02 and 0.01 for 1 versus 2 perforator flaps and 1 versus 3 perforator flaps, respectively). However, no significant differences were noted in fat necrosis, flap failure, and abdominal bulging rates across perforator groups. Additionally, flap weights were not significantly different across the three groups (Average: 1 perforator-774 grams, 2 perforators-797 grams, and 3 perforators- 749 grams). Neither perforator number nor nerve preserving techniques were found to result in significant decreases in abdominal bulge rates. CONCLUSIONS: Contrary to other studies, we found that the number of perforators harvested in DIEP flap breast reconstruction was not associated with increase or decrease in flap survival or fat necrosis. This occurrence could be attributed to the surgeons' choosing to proceed with single perforator flaps only when perforator size was adequately large, maintaining consistent blood supply. There was no association among perforator number, utilization of nerve sparing procedures, and abdominal bulge that required subsequent surgical intervention. Despite this, we still cautiously advocate nerve-preserving techniques that may have a subclinical effect.
Acceptability of Screening for Sexually Transmitted Infections in an Urban Pediatric Emergency Department in the Southern Region of the United States
(2016-01-19) Pfaff, Jamie; Johnson, Dawn
BACKGROUND: Adolescents age 13 to 24 years old are the demographic most affected by sexually transmitted infections (STIs) in the USA. The CDC, USPSTF and the AAP recommend screening sexually active females less than 25 years old in all health care settings for Neisseria gonorrhea (GC) and Chlamydia trachomatis (CT) and all high-risk females of this age group also for HIV and Syphilis. In regions with a high prevalence of STIs, such as Dallas County, the diagnosis and treatment of STIs is a vital step toward reducing the spread of these communicable diseases in this population. METHODS: All adolescents age 13-24 presenting to the Pediatric Emergency Department (PED) during the study period who met the study criteria were asked to participate. A total of 197 adolescents and 198 parents, 183 of which comprised parent-child dyads, were enrolled and completed separate surveys. Participants answered questions about adolescent and parent acceptability of STI screening, STI risk behaviors, and adolescents' history of STI screening and treatment. RESULTS: Analysis thus far shows that non-invasive STI screening is acceptable to the majority of both adolescents (70%) and parents (84%). Among patient/parent dyads, 59% had positive responses from both. No demographic factors demonstrated statistical significance. However, some factors displayed greater variability than others. In terms of age, adolescents greater than 15 years old were more likely to indicate acceptance of STI testing (73%) than those younger than age 15 (62%). Breakdown by adolescent race and ethnicity demonstrated a range of acceptability with 83% for those who identified as White or Caucasian, 59% for those identifying as Black or African American, 64% for those identifying as Hispanic, and 100% of the five participants identifying outside of the previous categories, "other". CONCLUSIONS: These acceptability results are similar to those found in a study performed in Jefferson County, AL where adolescents reported a 71% acceptance rate for GC and CT screening. This suggests that implementation of STI screening in the PED would be successful and well tolerated by the majority of adolescents and their parents. The variation in acceptability demonstrated by age and race were not statistically significant but may be useful in determining the minimum age of PED intervention and preparing culturally sensitive answers for questions from adolescents and patients in future testing interventions. Implementation of new PED HIV screening protocols are utilizing evidence based on this study and will further be assessed for continued improvement of Dallas adolescent health.
Acute Effect of High vs Low Dialysate Sodium on Endothelial Cell Function During Hemodialysis
(2013-01-22) D'Silva, Kristin; Molina, Christopher; van Buren, Peter; Kim, Catherine; Inrig, Jula
BACKGROUND: Intradialytic hypertension (HTN), a rise in blood pressure that occurs during hemodialysis (HD) treatments in up to 15% of patients, is associated with higher morbidity and mortality. The cause of intradialytic HTN is unknown but may be due to endothelial cell (EC) dysfunction. In vitro exposure of ECs to high sodium (Na+) concentration promotes EC stiffness and imbalances in vasoconstrictors (endothelin-1 [ET-1]) and vasodilators (nitric oxide [NO]). We hypothesized that, among patients with intradialytic HTN, exposure to high dialysate Na+ would lead to a decrease in NO and increase in ET-1 during HD. METHODS: We performed a 3-week, 2-arm, randomized crossover study among 16 HD patients with intradialytic HTN and compared the effects of high dialysate-to-serum Na+ gradients (5 mEq/L above participants' baseline Na+) vs low dialysate-to-serum Na+ gradients (5 mEq/L below baseline Na+ with lower limit of 134 mEq/L) on intradialytic changes in nitrite and ET-1. Differences between treatments were compared with repeated measures mixed linear regression and included randomization arm (high - low Na+ vs low - high Na+), treatment effect (high vs low Na+), subject, time and session. RESULTS: Study participants (N=16) had an average age of 58.8 years, 38% were black, 56% were Hispanic, and 94% were male. Intradialytic changes in NO and ET-1 with high and low dialysate-to-plasma Na+ gradients are shown in Figure 1. In the primary comparison of high vs low dialysate-to-serum Na+ gradient, there were no significant differences in intradialytic levels of NO or ET-1 (Table 1). However, when compared by randomization arm, participants who received the low dialysate-to-serum Na+ gradient followed by high compared to those who received the high dialysate-to-serum Na+ gradient followed by low had a significant decrease in ET-1 (parameter estimate -0.49 pg/mL, p=0.04) and significant increase in nitrite during hemodialysis (parameter estimate +0.16 nM, p=0.02) (Table 1). CONCLUSIONS: Patients who received the low dialysate-to-serum Na+ gradient before the high dialysate-to-serum Na+ gradient had higher levels of nitrite and lower levels of ET-1 throughout the three week study period compared to patients who received the high dialysate-to-serum Na+ gradient before the low dialysate-to-serum Na+ gradient. This suggests that the dialysate Na+ concentration may have longer-term effects on endothelial cell function.
Administration of Fatty Acid Emulsions to Reduce Secondary Brain Injury in Mice
(2018-01-23) Rodgers, Clifford; Chowdary, Ashish; Liu, Ming-Mei; Carlson, Deborah; Wolf, Steven E.; Minei, Joseph P.; Gatson, Joshua
BACKGROUND: Mild traumatic brain injuries are the most common type of injury to the head. Seventy-five to eighty percent of all traumatic brain injuries (TBI) are considered a mild TBI, or concussions, and involve only a short interruption of mental state and consciousness. Although the FDA reports no nutrition supplements for TBI therapy and/or symptom prevention, preclinical data has suggested that omega-3 poly unsaturated fatty acid (PUFAs) treatment decreases apoptosis, inflammation, and neurodegeneration following brain trauma. In this study, we hypothesized that Smoflipid® reduces inflammation in the brain of adult mice that have suffered a mild-to-moderate brain injury. Smoflipid® is an injectable liquid emulsion solution that contains omega-3, omega-6, omega-9, and medium chain triglycerides. METHODS: In this study, mice were subjected to a moderate brain injury using the controlled skull impact device (Leica microsystems) and we administered Smoflipid® intraperitoneally at day 1 and 3 after injury. At Day 14 after injury and treatment the mouse brains were harvested, processed, and stained using immunohistochemistry for the inflammatory markers, glial fibrillary acidic protein (GFAP) and Iba1. RESULTS: In this study after TBI, within the corpus callosum (C.C.) and cerebral cortex there was a significant increase in the levels of activated microglia (Day 14 p=0.05) compared to the control animals. Treatment with Smoflipid® shortly after injury, resulted in a significant decrease in the number of active microglia within these brain regions. CONCLUSIONS: Chronic activation of microglia and heightened inflammation in the cerebral cortex/C.C. after TBI, results in cognitive decline and long-term memory deficits. As a therapeutic strategy, by targeting these pro-inflammatory cells with Smoflipid®, we hypothesize that a reduction in the activity of microglia will improve results in better neurological outcomes. More definitive studies will be conducted to test the efficacy of Smoflipid® at reducing secondary brain injury after TBI.
The Adult Spina Bifida Patient: Does a Delay in Referral Impact Urodynamic Findings and Clinical Outcomes? Recommendations for Transition of Care
(2017-01-17) Eastman, Jessica; Lemack, Gary; Harris, Catherine; Howard, Catherine
INTRODUCTION: Improvements in the management of children with myelomeningocele have resulted in an influx of such patients, many of whom have complex neurogenic bladder conditions, to adult urologists. We reviewed the presenting symptoms, urodynamic findings, and changes in clinical management of adults with spina bifida, specifically focusing on the relationship between the delay in urological follow-up and clinical outcomes. METHODS: All patients with neurological conditions that presented for urologic evaluation at a tertiary referral center have been prospectively entered into a database since 2000. Data from patients with spina bifida including, bladder management, chief complaint, urodynamic findings (UDS), surgical interventions and upper tract imaging were analyzed. RESULTS: Of the 1110 patients in the database, 60 patients with spina bifida were identified (51.7% male, 48.3% female). Median age at presentation was 33 (16-64). The majority of patients presented for symptom evaluation (75%) vs. establishing care (25%). The most common presenting symptoms were incontinence (n=18, 30%) and urinary tract infection (UTI) (n=15, 25%). Patients who had documented prior urologic evaluation were assessed for the interval to presentation (n=53). Patients were classified as having their last evaluation within the preceding 12 months (n=23, 43.3%), between 12 and 24 months (n=17, 32%), between 2 and 5 years (n=11, 20.8%) or greater than 5 years prior (n=2, 3.8%). Patients were significantly more likely to present within 12 months of their last evaluation if they were symptomatic (p=0.022). Patients presenting more than one year from their last evaluation were more likely to have DO (p=0.0215), though neither altered compliance nor DESD were associated with delay in diagnosis. As seen with children, the UDS diagnosis of impaired compliance was significantly associated with abnormal imaging findings (p=0.0328). Overall, 42% of this cohort required intervention following referral, and urologic workup including urodynamics altered clinical management in 58.9% of patients. CONCLUSION: Spina Bifida patients continue to require close surveillance into adulthood, and this evaluation must include urodynamic testing. Additionally, there is indication that patients who delay care are more likely to have UDS abnormalities that might necessitate changes in management strategies. We advocate follow-up of less than 12 months between adult urology clinics or within one year after pediatric surveillance has terminated.
Alterations in Neural Stem Cell Fate Following Focal Ischemia
(2014-02-04) Nguyen, Derek; Vemireddy, Vamsidhara; Mashimo, Tomoyuki; Battiste, James; Maher, Elizabeth; Bachoo, Robert
INTRODUCTION: The purpose of this experiment is to determine the differentiation identity of the neural stem cells (NSC) in the subventricular zone (SVZ) of adult mouse brain after a middle cerebral artery occlusion (MCAO). Injury to the brain causes a large number of changes including inflammation and apoptosis, but the reaction of NSC's has been more difficult to characterize because of the transient nature of their response. Previously, adult neural stem cells (NSC) in the SVZ have been observed to differentiate predominantly into cells with neuronal characteristics. This theory is questioned via a tamoxifen-inducible cre-recombinase (Cre-ERT2) expression mouse model system. METHOD: The Cre-ERT2 expression mouse model system is driven by the Cystatin-C promoter to label NSC's in a time specific manner and track their cell fate after MCAO. After the ischemia, these brain sections were stained with different immunohistochemicals at three separate time points. One set was co-labeled with GFAP, an astrocyte marker, and BrdU, a proliferation marker. Another set was co-labeled with DCX, a neuronal marker, and BrdU. This was used to differentiate between latent NSCs and proliferating NSCs by comparing the ipsilateral side (ischemic) with the contralateral side (control) of the brain. RESULTS: Compared to the contralateral, the ipsilateral side had a significant increase in GFAP/BrdU positive cells between day 3 and day 7 time points. The cell quantity dropped between day 7 to day 14 time points. Compared to the contralateral, the ipsilateral side had a decrease in DCX/BrdU positive cells between day 3 and day 7 time points. The cell quantity significantly increased between day 7 to day 14 time points, and the quantity at day 14 was about twice to that of the day 3 time point. DISCUSSION: This data demonstrated that after the MCAO, the stem cells are not just undergoing neurogenesis, but are for certain period of time, also differentiating into astrocytes that are migrating towards the site of injury. This phenomenon is only witnessed in the NSCs towards the day 7 time point. Afterwards and leading up to day 14, the NSCs seem to be changing their cell fate programming from the astrocyte pathway back to the intended neuronal pathway. Thus, the staining results verify that after an ischemia, NSCs within the SVZ regions of the brain undergo a constant change of programmed cell fate, alternating between immature neurons and astrocytes implicating future aims for "programmed" neurogenesis in the development of therapeutic strategies for the treatment of brain damage and disease.
Altered Atrial Remodeling in the Muscular Dystrophies
(2019-01-22) Kappalayil, Anishka; Patel, Vishal; Cheeran, Daniel; Tassin, Tara C.; Zaha, Vlad; Peshock, Ronald M.; Mammen, Pradeep P. A.
INTRODUCTION: Muscular dystrophies (MD) are genetic disorders that cause progressive peripheral skeletal myopathies. The specific mutations lead to a cycle of muscle degeneration and regeneration in MD patients, ultimately producing progressive skeletal muscle wasting. Many of the MD patients also develop associated cardiomyopathies and in 2018 is the leading cause of death. Our group has demonstrated that MD patients have very small left ventricular (LV) masses as well as depressed LVEF. This data suggest that the mode of maladaptive cardiac remodeling may be different in MD vs NICM patients. However, it remains unknown the degree of atrial remodeling that occurs in MD patients. Therefore, the central hypothesis of this study is that atrial remodeling in MD patients is altered in comparison to non-ischemic cardiomyopathy patients. METHODS: Utilizing the UTSouthwestern Cardiomyopathy Clinic, MD and NICM patients were identified. Data was extracted from cardiac MRIs to measure left atrial (LA) volumes and function. The variables used were the LA end systolic volume (LA-ESV), LA end diastolic volume (LA-EDV), and LA ejection fraction (LAEF). These measures were normalized to the body surface area (BSA). We collected data on 78 MD patients (33 MD females, 45 MD males) and 80 NICM patients (28 NICM females, 52 NICM males). Utilizing unpaired two-sided T-test, LA data was analyzed between the matched MD and NICM patients. RESULTS: The MD and NICM patient cohorts showed significant differences in the LA structure and function. CONCLUSION: Collectively, the data suggests alternative mode of maladaptive cardiac remodeling in MD vs NICM patients. Thus, further investigation into the mechanism that leads to MD-associated cardiomyopathy may ultimately identify novel therapeutic targets for the amelioration of this disease entity.
Analyses of the Link Between Amyloid and Tau Pathology in an AD Mouse Model (3xtg-AD): Disease Progression with Increased Levels of Abeta and Tau Peptides
(2018-01-23) Zapata, Lucio, Jr.; Ismail, Hannah; Lambracht-Washington, Doris
INTRODUCTION: Pathological features of Alzheimer's disease (AD) include the accumulation of extracellular amyloid plaques composed of aggregated amyloid-β (Aβ) peptide and intracellular neurofibrillary tangles consisting of phosphorylated tau protein. Mutations in the genes that encode amyloid precursor protein (APP), and presenilin 1 and 2 (PS1/PS2) have been shown to cause familial AD in humans. Studies provided evidence that Aβ accumulation may initiate phosphorylation of tau protein, via the Ras/MEK/Extracellular Signal-regulated Kinase (ERK) signaling cascade, activation of the mitogen-activated protein kinase (p38 MAPK), Cyclin dependent kinase 5 (CDK5) and/or glycogen synthase kinase-3β (GSK3β). We studied distribution of Aβ and tau oligomers, Erk activity in different brain lysate fractions from different age groups of a triple transgenic mouse model (3xTg-AD) and wild-type mice, and Erk activity in DNA Abeta42 immunized mice. METHODS: Brain lysates of 4-, 6-, 12-, and 20-month-old 3xTg-AD and wild-type mice were prepared via a 4-step extraction protocol in TBS (soluble), TBS-T, SDS, and formic acid. DNA Abeta42 vaccination administered via gene gun. Abeta and Tau concentrations and Tau phosphorylation levels were monitored by Dot blot, Semidenaturing detergent agarose gel electrophoresis (SDD-AGE), and ELISA using anti-Abeta and anti-Tau antibodies. Erk1/2 levels were monitored by Western blot using monoclonal antibodies. RESULTS: There was a significant increase of total tau concentrations with increasing age and we found also an increasing insolubility (more tau in the non-soluble brain lysate fractions). 4- and 20-month-old 3xTg-AD soluble brain lysates indicated the presence of aggregated tau peptide, which was not present in wild-type control mice. Kinases involved with tau phosphorylation were measured and showed an increase of activated/phosphorylated Erk1/2 with increasing age, with a drop in concentration at 12 months in half of the mice analyzed (n=5). Immunized 3xTg-AD mice showed a decrease in activated Erk1/2 when compared to non-immunized, age matched mice. DISCUSSION: The 3xTg-AD mouse model provides a good model to study pathologies and possible treatments for human Alzheimer's disease. Abeta 42 peptide and tau increase due to age in this mouse model. A link between the amyloid pathology is likely found in the wide spectrum of cellular kinases which are upregulated due to Abeta in Alzheimer's disease. Therefore, immunization against Abeta and generation of anti-Abeta antibody will indirectly reduce tau pathology.
Analysis of Association Between Keloids and Other Medical Conditions
(2016-01-19) Rutherford, Audrey; Glass, Donald A., II
BACKGROUND: Keloids are an exaggerated response to cutaneous wound healing. Keloids negatively affect patients' quality of life and there is no 100% effective treatment to prevent occurrence or recurrence. Previous results from the Genetic Causes of Keloid Formation Study (GCKFS), an IRB-approved keloid registry, showed that hypertension and obesity may be more prevalent in African-Americans with keloids versus the general African-American population. This suggests that there are possible common mechanisms between keloids and these comorbidities. OBJECTIVE: The aim was to assess for an association between hypertension and/or obesity with keloid-affected patients, and to evaluate various subcategories of keloid-affected patients. METHODS: Seventy-nine GCKFS participants with diagnosed keloids were matched to controls from the Dallas Heart Study (at a 1 GCKFS:7 DHS ratio). Participants were categorized into hypertensive and obese cohorts using objective recorded measurements and calculations made using Fisher's exact test (significance P < 0.05). Sub-analyses were assessed among the GCKFS cohort using number of keloids, location, and number of anatomic sites involved. RESULTS: There were 504 total keloids distributed among six designated anatomical sites (ears, neck up, extremities, trunk, abdomen, other). Thirty (37.97%) GCKFS participants were hypertensive, and thirty-six (45.57%) were obese. The GCKFS participants showed an association with hypertension (p=0.045) but not with obesity (p=0.903). On subanalyses, keloid-affected individuals under age 30 had a higher prevalence of hypertension (p=0.042) and participants with multiple keloid sites had a higher prevalence of obesity (p=0.024). CONCLUSIONS: The results are consistent with hypertensive associations with keloids found in the literature. Data collection will continue by increasing the GCKFS cohort to determine if the trending data will reach statistical significance. Further research is encouraged to delve into the mechanisms between the association between hypertension and/or obesity and keloids.
Analysis of Free Flap Breast Reconstruction Failures: Are Specific Patient Characteristics Associated with Free Flap Failure?
(2013-01-22) Sciano, Natalie M.; Farkas, Jordan; Cortez, Robert; Miller, Travis; Davis, Kathryn; Kenkel, Jeffrey M.
PURPOSE: This study was performed to gain insight on the patients who have undergone free flap breast reconstructive surgery. Recognizing certain patient variables, as risk factors for developing free flap failure, is invaluable. This knowledge can provide surgeons the benefit of foresight when assessing patients pre and postoperatively. The goal was to identify specific characteristics that predisposed patients to developing flap failure. METHODS: A retrospective chart review was completed on patients who had received free flap breast reconstructive surgery during January 2008 to January 2012. A cohort of 124 patients receiving free flap reconstruction was identified using the Current Procedural Technology (CPT) code 19364. A number of patient variables which include general characteristics, comorbidities, and surgical characteristics were analyzed to determine their contribution toward a patient's development of free flap failure. Patients were categorized into two groups- those without and those with flap failure. A comparison of the means and proportions was performed to determine statistical significance between the two groups. The level of statistical significance for this univariate analysis was set at a P < 0.05. RESULTS: All of the 124 patients identified were female. The overall flap success rate was 91.94 percent, with only ten patients experiencing flap failure. Of the factors analyzed in this study, there was not an identified patient characteristic that predisposed a patient to developing free flap failure. CONCLUSIONS: Flap failure is an unfortunate risk of reconstructive surgery that needs to be minimized at all costs. No specific patient variables were identified as predisposing risk factors that could contribute to free flap failure. Institutions should strive to educate all breast reconstruction candidates on their options and risks which can help increase the volume of patients acquiring reconstruction. In the future, other investigations with a larger sample size should be done to yield more beneficial information for the physician and patient.
Analysis of Resident Conducted Social Determinants of Health Informed Home Visits
(2020-01-21) Cline, Matthew; Day, Philip; Gimpel, Nora; Pagels, Patti
CONTEXT: Home visits can improve quality of care, save money, improve health outcomes, and provide a unique opportunity for residents to learn more about patients' social context and assess the various social determinants of health (SDH) that impact patients' health and wellbeing. In order to facilitate a SDH-focused visit, the Department of Family and Community Medicine at UT Southwestern implemented a brief SDH questionnaire in all home visits. OBJECTIVE: The objective of this study is to assess patient self-reported SDH and resident reflections on patient social status, the utility of a SDH survey during home visits, and resident comfort levels with addressing patient SDH HUMAN SUBJECTS REVIEW: This study was approved as an "exempt" study by the UTSW IRB DESIGN: Mixed methods pilot study utilizing patient self-reported data and open- ended reflection questions SETTINGS: Home health visits for patients from an urban safety-net clinic in Dallas, TX. Participants: Adult patients >18 years of age, selected by the resident INTERVENTION/INSTRUMENT (AS PERTINENT): Quantitative survey domains include: demographics, financial status, social support, safety, employment, and living conditions. Open response questions queried resident impressions of the survey, comfort during the interview, new insights about the patient, impact on future practice, and ability to address SDH concerns. ANTICIPATED RESULTS: 42 surveys collected from 42 home visits. Most patients were female (61.9%) and African-American (45.2%), aging from 25 to 88 years (mean=60.24). Prevalence of adverse SDH were relatively low. Common themes of resident responses: positive utility of the survey as a guide for understanding and assessing patient SDH; wide variation in comfort level when inquiring about patient SDH with positive influence from prior experience, assistance from colleagues, or prior good relations with patients; and expressed intention to include SDH assessment in their continuing career. CONCLUSIONS: Residents recognized the value of assessing SDH during home visits and expressed implement a standardized process for selecting patients for home visits as this was largely left to the discretion of the resident. More thorough assessment of patient SDH may help to craft a more robust and standardized system to prioritize patients that would most benefit from receiving home visits.
Anterior Cruciate Ligament Tears: Impact of Delayed Presentation on Intra-Articular Injuries
(2016-01-19) Chavez, Audrie; Riepen, Dietrich; Coyner, Katherine J.; Schell, Benjamin; Khazzam, Michael
BACKGROUND: Chronic anterior cruciate ligament (ACL) injury is associated with increased risk for meniscal and chondral injuries. This study aims to establish specifically what meniscal and chondral injuries occur in the setting of chronic ACL deficiency. UTSW and Parkland treat many chronically ACL-deficient patients, thus offering unique insight into the natural history of ACL-deficient knees. METHODS: Retrospective chart review was conducted for all patients who underwent ACL reconstruction at UTSW or Parkland from 1/1/2009 to 5/4/2015. Variables studied were age, gender, BMI, chondroplasty performed, microfracture performed, medial meniscus tear (MMT), lateral meniscus tear (LMT), and injury to the medial femoral condyle (MFC), lateral femoral condyle (LFC), medial tibial plateau (MTP), lateral tibial plateau (LTP), and patellofemoral (PF) joint. RESULTS: Four hundred and ten subjects were included in this study. Average patient age was 27+8.8 years. 58.5% had BMI >25. Males comprised 70.5% of patients. Approximately 27.1% received surgery less than 3 months after injury, 23.4% from 3 to < 6 months, 17.8% from 6 to < 12 months, 23.9% from 12 to < 60 months, and 6.8% 60+ months. Male gender and older age were predictive factors for delayed reconstruction (P<.01). MMTs were correlated with both MFC injury (OR 4.8) and MTP injury (OR 2.6), while LMTs were only correlated with LTP injury (OR 2.0). Frequency of MMT was increased with surgical delay. Compared to delays of 0 to less than 3 months, MMTs were more common in patients with delays of 6 to < 12 months (OR 2.1), 12 to < 60 months (OR 4.2) and 60+ months (OR 6.2). A similar trend characterized MFC injury. Compared to the 0 to < 3 month group, MFC injury was more likely to occur with delays of 6 to < 12 months (OR 2.7), 12 to < 60 months (OR 3.1), and 60+ months (OR 8.3). LTP and LFC injury were only associated with surgical delays of 12 to < 60 months (P<.05) and 60+ months (P<.001). Microfracture and chondroplasty were more likely to be performed in patients with delays of 12 to < 60 months (P<.001). CONCLUSION: Delaying ACL surgery for 6 months or longer is associated with an increased presence of medial meniscus tears and chondral injury (MFC, LFC, and LTP), with increased incidence in longer delays. This data supports not delaying surgery more than 6 months following an ACL tear to prevent the incidence of secondary meniscus tears and articular cartilage injury. In addition, particular attention should be paid to those who are of older age and male gender as they are at increased risk for worse cartilage and meniscus injury.
Anti-VEGF Induced Reduction in Microvessel Density Does Not Correlate with Anti-Tumor Repsonse in Lung Cancer Xenografts
(2013-01-22) Jacob, Antonia J.; Sullivan, Laura A.; Toombs, Jason E.; Minna, John D.; Brekken, Rolf A.
Vascular endothelial growth factor-A (VEGF) is a primary stimulant of angiogenesis in pathological conditions including tumor progression. Strategies to block VEGF activity prevent or slow tumor growth in preclinical settings; however, clinical studies with bevacizumab, a monoclonal antibody (mAb) specific for VEGF have resulted in only modest benefit to a subset of patients with lung cancer. Previous studies in our laboratory defined the therapeutic efficacy of bevacizumab and an alternative anti-VEGF mAb (r84) in 12 non-small cell lung cancer (NSCLC) xenografts. Three NSCLC xenografts (Calu-6, A549 and Calu-3) showed intrinsic resistance to bevacizumab therapy. In the present study we evaluated whether microvessel density (MVD) could be used to 1) demonstrate if the anti-VEGF mAbs were effective at reducing VEGF-driven angiogenesis and 2) if MVD changes induced by bevacizumab or r84 correlated with overall therapeutic efficacy as determined by tumor size after chronic therapy. 3-5 tumors from animals bearing NSCLC xenografts treated with a control mAb (XTLl, bevacizumab or r84 were evaluated by immunohistochemistry for endothelial cells as a measure of microvessel density. Two independent endothelial cell markers were used, endomucin and CD31. In 11 of the 12 xenografts treatment with bevaclzumab or r84 significantly reduced MVD compared to XTL treatment, suggesting that bevacizumab and r84 do reduce VEGF-driven angiogenesis. However, the reduction in MVD induced by anti-VEGF therapy did not correlate with overall tumor response to therapy. These results strongly implicate resistance to anti-VEGF therapy is not mediated by activation af alternative angiogenic programs to compensate for VEGF blockade. Further the results suggest that tumor cell adaptation to therapy-induced hypoxia underlies poor therapeutic response to anti-VEGF strategies. Microarray of gene expression analysis of control treated tumors revealed several genes associated with metabolism, proliferation, and metastasis were significantly increased in tumors that displayed intrinsic resistant to bevacizumab. We conclude that response of tumor cells to therapy-induced hypoxia is a critical feature that drives the overall efficacy of anti-VEGF strategies.
Anticoagulant Use is Associated with Improved Biochemical Control of High-Risk Prostate Cancer Patients Treated with Radiation Therapy
(2013-01-22) Jacobs, Corbin; Kim, D. Nathan; Choe, Kevin; Yan, Jingsheng; Xie, Xian-Jin; Hannan, Raquibul; Pistenmaa, David; Lotan, Yair; Roehrborn, Claus
INTRODUCTION: The coagulation system modulates multiple cancer pathways, including tumor proliferation, angiogenesis, host immunologic defense, and metastasis. Prior studies have reported improved survival and freedom from biochemical failure (FFBF) in prostate cancer (PCa) patients taking aspirin and other anticoagulants (ACs). We reviewed the outcomes of patients with high-risk PCa who received ACs and definitive radiation therapy (RT). METHODS: Patients with nonmetastatic high-risk adenocarinoma of the prostate (stage ≥ T3a, or Gleason score (GS) ≥ 8, or prostate-specific antigen (PSA) ≥ 20) treated with definitive RT between 2005-2008 at UTSW were identified. The AC group consisted of patients who had warfarin, clopidogrel, or aspirin recorded on the medication list at any clinical visit. FFBF of patients was determined using the Phoenix definition. Log-rank test was used to correlate FFBF with the ACs. Univariate and multivariate analysis (MVA) of FFBF to pretreatment PSA, GS, stage, hormone use, total RT dose, and ACs was performed. RESULTS: Among the 76 patients identified, 45 (59.2%) comprised the AC group. Within the AC group, 43 were taking aspirin, 8 were taking warfarin, 8 were taking clopidogrel, and 13 were taking multiple ACs. Median follow up was 61.2 months (range 3.1-89.4) for the AC group and 55.1 months (range 6.5-88.9) for the non-AC group. Patients receiving ACs exhibited significantly improved FFBF compared to the control group (p=0.0018; log-rank test). The estimated 4-year FFBF was 83.7% and 63.2% for the AC and non-AC groups, respectively. Among the patients taking a single AC, only aspirin showed significantly improved FFBF (p=0.0037). The hazard ratio for T-stage was 1.18 (95% CI 0.75, 1.85; p=0.4672) in the AC group and 1.67 (95% CI 1.09, 2.58; p=0.0196) in the non-AC group, implying a benefit from taking the AC. Aspirin use, T-stage, and N-stage remained significantly correlated to FFBF (p=0.0002, p=0.0056, and p=0.0040, respectively). The early and late grade 2 toxicity rates for rectal bleeding were 7.7% in patients on multiple ACs and 0% for patients on a single AC or no AC. No patients experienced grade 3 rectal toxicity. CONCLUSION: Use of ACs in high-risk PCa patients improved the FFBF after definitive RT without increasing rates of rectal bleeding. This suggests that daily use of a single anticoagulant, especially aspirin, in high-risk PCa patients treated with definitive RT decreases biochemical failure and may improve outcome. Large prospective data are needed to validate the findings of this study.
Antigen-Specific Natural Killer Cell Responses in Chronic Hepatitis C Virus Infection
(2014-02-04) Bowman, Kathryn; Holz, Lauren; Rehermann, Barbara
Chronic hepatitis C virus (HCV) infection results in an inflammatory liver disease leading to fibrosis and cirrhosis. The progression of liver disease is thought to be immune-mediated because HCV itself is non-cytopathic. Given that HCV-specific T cells are diminished in number and functionally exhausted in chronic HCV infection, it remains unclear which cell population drives disease pathogenesis. Here, we investigated the function of natural killer (NK) cells, the major innate immune cell population in the liver. The NK cell population increases further in the setting of chronic hepatitis C infection and have multiple mechanisms of cytotoxicity. We investigated whether NK cells could respond to HCV in an antigen-specific manner. PBMCs from 39 patients with chronic HCV infection (gt 1) not recently on medication (>2 years) were stimulated for 8 hours in a whole blood activation assay with pools of overlapping 18-mer peptides comprising HCV structural (E1, E2) and nonstructural (NS3) proteins. Cytokine production by NK cells and T cells was assessed by multicolor flow cytometry. The frequency of IFN-γ+ NK cells was 5 fold greater than the frequency of IFN-γ+ T cells. A minority of IFN-γ+ NK cells co-produced TNF-α. NK cell responses to HCV peptides varied between subjects, but did not correlate with T cell responses or viremia. This study demonstrates that NK cells are activated in an antigen-specific manner in chronic HCV infection and respond to both structural and nonstructural HCV proteins. Natural killer cell cytokine and cytotoxic responses were larger than corresponding T cell responses. The mechanism of antigen-specific NK cell activation is currently under investigation.
Antisense Blockade of Efflux Systems in Gram-Negative Pathogens
(2018-01-23) Subramanian, Naveen G.; Felder-Scott, Christina F.; Sturge, Carolyn R.; Greenberg, David
Antibiotic resistant bacteria, aka "super bugs", are a critical threat to public health worldwide, as the medical community is running out of effective antibiotics against a growing number of bacteria. One of the ways that bacteria develop resistance to antibiotics is by utilizing efflux systems that are used to pump the antibiotic out. A strategy that is currently being investigated is to restore the susceptibility of these bacteria to antibiotics by using peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) to suppress genes within these bacteria that encode components of efflux pumps. This project studied the effectiveness of PPMOs that target the AcrAB-TolC efflux pump, which is a major component of the intrinsic antibiotic resistance mechanisms of E. coli and K. pneumoniae. Experiments tested for the effect of the PPMO targeting the acrA gene, specific sequences within the acrA gene, and the tolC gene. The effect of the PPMO was measured by a change in the minimum inhibitory concentration (MIC) of common antibiotics such as Piperacillin/Tazobactam (Pip/Tazo), Azithromycin, and Levofloxacin on strains of these two bacteria. The results show that PPMOs targeted to the acrA gene have a 4-8 fold effectiveness at lowering antibiotic MICs for the bacterial strains. PPMOs that targeted the tolC gene, on the other hand, have no synergistic effect in lowering antibiotic MICs for the bacterial strains. In addition, changing the sequence of the PPMOs targeting the acrA gene was shown to have an effect, albeit small, on susceptibility to antibiotics, which suggests that targeting specific regions of a gene of interest can induce more or less susceptibility in the bacteria to antibiotics.
Apolipoprotein E Isoform Influence on Outcomes after Pediatric Traumatic Brain Injury
(2016-01-19) Usala, Claire; Huang, Rong; Hernandez, Ana; Miles, Darryl
INTRODUCTION: The ε4 allele of the apolipoprotein E gene (APOε) is associated with poor outcomes in adults with traumatic brain injury (TBI), but its influence on recovery after pediatric TBI is uncertain. The primary aims of this study were to determine if an association exists in the outcome of children after TBI between those with at least one ε4 allele and non ε4 genotypes. Using the Glasgow outcome score (GOS), we examined three outcome variables between the two groups 1) GOS at hospital discharge, 2) GOS at long-term follow-up, and 3) the magnitude of change in GOS from discharge to > 6 month assessment (Δ GOS). METHODS: Data were prospectively collected from 220 children presenting with moderate or severe blunt head trauma between the ages of 0 and 17 years old from 2002-2013. Outcomes were assessed at hospital discharge and 12.7±8.4 months post-injury. Patients in the ε4 and non ε4 groups did not differ in injury mechanism, severity, or demographics; 23.4% had at least one ε4 allele and ε3/ ε3 was the most common genotype (67.4%). Multiple regression model analysis was conducted to determine if associations existed between the genotype combinations and outcome while controlling for age, ER GCS, ICP monitor placement, and whether CPR was performed. For ε4 genotypes analysis, we also stratified patients by admission Glasgow Coma Scale (GCS) into severe (GCS 3-8) versus non-severe (9-15), as well as moderate and severe (3-12) versus mild (13-15) groups. RESULTS: For aim 1, the GOS at discharge did not differ significantly in ε4 versus non- ε4 patients in any injury severity category before or after controlling for cofounding variables. However, after controlling for confounding variables, patients with at least one ε2 allele in the moderate or severe injury category had significantly worse GOS at discharge. For aim 2, after controlling for confounding variables, patients with the ε3/ε3 genotype had significantly better long-term GOS than patients with the genotype ε3/ε2 (p<0.05). However, we did not find a significant difference in long-term outcome between ε4 and non ε4 genotypes in the primary analysis or when stratified by injury severity groups. Finally, between ε4 and non ε4 genotypes, the Δ GOS and neuropsychological scores did not differ significantly between genotypes. DISCUSSION: Overall these results propose that unlike adults, the ε4 allele may not be associated with 12-month outcome or the rate of recovery (ΔGOS) from hospital discharge following pediatric TBI. Our results implicating worse outcomes for the ε2 genotypes suggest that this allele may be a candidate for further study to delineate its role in TBI outcome in children. Unique to this study was our analysis of neuropsychological measures, which were also not affected by the presence of ε4 in a smaller cohort of children. This study adds to current literature suggesting that unlike adults APOε4 may not exert a significant effect on pediatric TBI outcome. However, these results are limited in that any genotypic effect on neurologic repair may not be apparent for much longer time periods in pediatric brain injury as the child continues to develop and grow.
Application of the "Hybrid Approach" to Chronic Total Occlusions in a Contemporary Multicenter US Registry
(2014-02-04) Menon, Rohan; Christopoulos, Georgios; Karmpaliotis, Dimitrios; Alaswad, Khaldoon; Lombardi, William; Grantham, Aaron; Mishoe, Katrina L.; Patel, Vishal G.; Rangan, Bavana V.; Kotsia, Anna P.; Lembo, Nicholas; Kandzari, David; Lee, James; Kalynych, Anna; Carlson, Harold; Garcia, Santiago; Banerjee, Subhash; Thompson, Craig A.; Brilakis, Emmanouil S.
BACKGROUND: The "hybrid" approach to coronary chronic total occlusion (CTO) crossing was developed to optimize procedural efficacy, efficiency, and safety. Current strategies of crossing CTOs include antegrade wire escalation, antegrade dissection re-entry, and the retrograde approach. The "hybrid" approach is an algorithm that, based on angiographic characteristics of the lesion, streamlines the selection of the optimal technique for crossing the CTO. The goal of this study was to analyze the impact of the "hybrid" approach to CTO percutaneous coronary intervention on procedural workflow and outcomes at five high-volume US centers. METHODS: We examined the procedural techniques and outcomes of 489 consecutive CTO cases performed using the "hybrid" approach between 2012 and 2013 at 5 US centers from cities including Appleton WI, Atlanta GA, Bellingham WA, Kansas City MO, and Dallas TX. RESULTS: Mean age was 63.8 ± 9.8 years and 86.9% of the patients were men, with high prevalence of diabetes mellitus (41.7%) and prior coronary artery bypass graft surgery (35.7%). Most target CTOs were located in the right coronary artery (61.5%), followed by the left anterior descending artery (20.9%) and left circumflex (16.8%). Dual injection was used in 73.3%. Overall, antegrade wire escalation was used in 62.8%, antegrade dissection re-entry in 38.9% and retrograde in 44.2%. Among successful cases, the final successful crossing technique was antegrade wire escalation in 40.6%, antegrade dissection and re-entry in 27.5%, and retrograde in 31.9%. The initial crossing strategy was successful in 62.0% of the patients, whereas 35.8% required an additional 1 to 4 crossing strategies. Technical success was achieved in 91.6% and major procedural complications occurred in 1.6%. Mean contrast volume, fluoroscopy time, and air kerma radiation exposure were 297.6 ± 154.7 ml, 48.9 ± 31.4 min, 4.4 ± 3.8 Gray, respectively. CONCLUSION: Application of the "hybrid" approach to CTO crossing resulted in high success and low complication rates among a varied operator group and hospital structure, further supporting the value of the "hybrid" approach in crossing these challenging coronary lesions.

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